Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials

Vergote, Ignace; Coens, Corneel; Nankivell, Matthew; Kristensen, Gunnar B.; Parmar, Mahesh; Ehlen, Tom; Jayson, Gordon C.; Johnson, Nick; Swart, Ann Marie; Verheijen, René H.M.; McCluggage, W. Glenn; Perren, Timothy J.; Panici, Pierluigi Benedetti; Kenter, Gemma G.; Casado, Antonio; Mendiola, C.; Stuart, Gavin; Reed, Nick; Kehoe, Sean; G., Claes Tropé; Dobbs, Stephen; Essapen, Sharadah; Hoskins, P.; Green, John; Gilby, Edward D.; Baal, M. van; Twigg, Jeremy; Burg, M.E.L. van der; Godfrey, Keith; Lacave, Ángel J.; Angioli, Roberto; Nath, Rahul; Chin, K. A. J.; Lotocki, Robert; Olaitan, Adeola; Mosgaard, Berit Jul; Rustin, G. J. S.; Ind, Thomas; Hogg, Martin; Velden, J. Van Der; Ledermann, Jonathan A.; Sykes, Peter; Madhavan, Krishnawam; Kannisto, Päivi; Hird, V.; Evans, Allyson; R., R. Sandvei; Gauthier, Philippe; Cruickshank, D.J.; Ottevanger, P.B.; Pearson, Sheila E.; Kitchener, Henry C; Hall, Marcia; Bessette, Paul; Pecorelli, Sërgio; Gerdin, Eva; Lopes, Tito; Fish, Andrew; Barlow, Clare; Eygen, Koen Van; Floquet, Anne; Tholander, Bengt; Gül, Nurdan; Gornall, Robert; Kirwan, P. H.; Symonds, Paul; Hoggart, Richard; McNeish, Iain A.; Hocking, M A; Sammaraie, Al; Speiser, Paul; Leblanc, Éric; Green, J.A.; Oliveira, C Fernández; Grimshaw, Robert; Zola, Paolo; Parkin, David E.; Luesley, David; Lamb, Martin; Hamid, Abdel; Ahmed, Ahmed; Plante, Marie; Valk, B. De; Nordin, Andy; Clamp, Andrew R.; Pérez, David Díaz; Dark, Graham; Ferguson, Michelle; MacGregor, Carol; Skailes, G.; Jones, Rachel; Gillespie, Alan; Cawdell, G.; Leeson, Simon; Elit, Laurie; Dittrich, Christian; Gotlieb, Walter H.; Poole, David; Cullimore, J.; Crosse, Barbara; Ridley, Paul; Head, A; Nieto, Joaquín J.; Awwad, S.; Brinkmann, Dirk; Eustace, D.; Hindley, Andrew; Katsaros, Dionyssios; Popadiuk, Catherine; Kristeller, Tome; Redman, C. W. E.; CHAN, Samuel; Marth, Christian; Yiannakis, Dennis; Lankaster, Kate; Beynon, Gareth; Suhail, Anwar; Fernando, Indrajit; Hong, Anne; Quigley, Mary; Adeyemi, Olu; Persic, Mojca; Lofts, F.; McNally, Orla; Tristam, Amanda; Lee, Martin; Counsell, R.; Gleeson, Noreen; Papadopoulos, A.; Maggino, T; Honkoop, AH; Ghatage, Prafull; Vermorken, Jan B.; Grève, Jacques De; Boman, Karin; Petru, Edgar; Amant, Frédéric

doi:10.1016/s1470-2045(18)30566-7

Cited by 200 publications

(129 citation statements)

References 17 publications

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“…Moreover, by analyzing separately patients with primary high-grade serous ovarian cancer, we found, as already reported in the literature 4 , that OS and PFS were not significantly different among patients who underwent optimal cytoreductive surgery compared to patients who underwent diagnostic/minimally cytoreductive surgery [median OS: 28.3 (range 3-60) vs 27.6 (range 5-60) months (95% CI −11.81-13.28; p = 0.514); median PFS 18.5 (range 3-60) vs 16 (range 5-45) months (95% CI −4.75-16.84; p = 0.786), respectively], yet OS and PFS was correlated with the M1 percentage and ratio in both groups (Fig. 2).…”

Section: Resultssupporting

confidence: 82%

“…The identification of predictive markers for chemotherapy sensitivity or resistance is crucial for choosing the most appropriate management strategy for ovarian cancer patients. In fact, maximal cytoreduction seems to offer the highest advantage in terms of PFS and OS only in chemoresistant tumors 4 . In this regard, emerging evidence from Thorsson et al 1 that found that M1 macrophage polarization, in the context of a peculiar immunological phenotype found in ovarian cancer patients, was associated with improved survival, was of great clinical relevance.…”

Section: Discussionmentioning

confidence: 99%

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Role of M1-polarized tumor-associated macrophages in the prognosis of advanced ovarian cancer patients

Macciò

Gramignano²,

Cherchi

et al. 2020

Sci Rep

111

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The identification of prognostic and predictive markers is crucial for choosing the most appropriate management method for ovarian cancer patients. We aimed to assess the prognostic role of tumorassociated macrophage (TAM) polarization in advanced ovarian cancer patients. We carried out a prospective observational study that included 140 consecutive patients with advanced-stage highgrade serous ovarian cancer as well as patients with other histotypes of ovarian cancer and patients with ovarian metastasis from other sites between June 2013 and December 2018. Patients were enrolled at the time of laparoscopic surgery before receiving any antineoplastic treatment. We found that patients with high-grade serous papillary ovarian cancers had a prevalence of M1 TAMs, a higher M1/M2 ratio, and a longer overall survival (OS) and progression-free survival (PFS) than other patients. Regression analysis confirmed that there was a significant positive association between the M1/M2 ratio and an improved OS, PFS and platinum-free interval (PFI), both in the entire population and in patients stratified according to tumor type and initial surgery. Kaplan-Meier analysis was performed after the patients were divided into 2 groups according to the median M1/M2 ratio and revealed that patients with a high M1/M2 ratio had a higher OS, PFS and PFI than those with a low M1/M2 ratio. In conclusion, the prognostic and predictive role of TAM polarization in the tumor microenvironment could be of great clinical relevance and may allow the early identification of patients who are likely to respond to therapy. Further studies in a larger prospective sample are warranted.www.nature.com/scientificreports www.nature.com/scientificreports/ linear relationship (β coefficient = 0.504, 95% CI 0.493-10.334, p = 0.033) was found between the platinum-free interval and M1/M2 ratio (Fig. 2).The median value for the M1/M2 ratio was 1.4. Then, we analyzed the difference in OS and PFS by Kaplan-Meier curve analysis and log-rank analysis between patients with an M1/M2 ratio ≥ 1.4 and those with an M1/M2 ratio < 1.4. We found that patients with an M1/M2 ratio ≥ 1.4 had a significantly longer OS (34 months versus 18 months, HR 2.7483, 95% CI: 1.1667-6.4736; p = 0.0207), PFS (24 months versus 9 months, HR 2.1285, 95% CI: 1.0461-4.3309; p = 0.0371) and PFI (12 months versus 6 months, HR 3.3959, 95% CI 1.2471-9.2469; p = 0.0168) ( Fig. 3). Scientific RepoRtS |(2020) 10:6096 | https://doi.

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Section: Resultssupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Role of M1-polarized tumor-associated macrophages in the prognosis of advanced ovarian cancer patients

Macciò

Gramignano²,

Cherchi

et al. 2020

Sci Rep

111

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“…The goal of CRS is to achieve a resection that leaves no gross residual disease because this has been shown to correlate with survival (Table 1). 12,20,21 …”

Section: Principles Of Surgerymentioning

confidence: 99%

“…Microscopic residual disease after surgery was still associated with a longer median overall survival (OS). Survival results favored neoadjuvant chemotherapy for women with stage IV disease and upfront debulking for women with stage III disease and upper abdominal metastases smaller than 5 cm; however, this was not a primary outcome measure of either of these trials 21 …”

Section: Principles Of Surgerymentioning

confidence: 99%

The Chicago Consensus on peritoneal surface malignancies: Management of ovarian neoplasms

Hoppenot¹,

Schuitevoerder²,

Izquierdo³

et al. 2020

Cancer

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The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of ovarian neoplasms specifically related to the management of peritoneal surface malignancy. These guidelines are developed with input from leading experts, including surgical oncologists, medical oncologists, gynecologic oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence. Cancer 2020;126:2553-2560. Communication 2554Cancer June 1, 2020 seeding and upstaging of a potentially early-stage cancer. The most common histologic diagnosis is high-grade serous cancer (66% of EOCs), with mucinous cancer, endometrioid cancer, and carcinosarcoma each accounting for about 10%. Clear cell carcinoma and low-grade serous carcinomas are less frequent, accounting for less than 5% of the remaining cancers, and have a strong association with endometriosis and borderline tumors, respectively. Pathological diagnosis should be verified by an experienced gynecologic pathologist and confirmed by immunohistochemical markers that can help to distinguish ovarian cancer from cancers metastatic to the ovary (eg, CK7, CK20, CA125, CEA, WT1, PAX8, p53, estrogen receptor/progesterone receptor). Accurate identification of low-grade serous carcinomas is See companion articles on pages

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“…HGSC frequently presents at advanced stage, and complete resection of all macroscopic disease is the single most important prognostic factor in advanced ovarian cancer. Neoadjuvant chemotherapy (NACT) followed by debulking surgery has been shown to have similar progression‐free survival (PFS) and overall survival (OS) as upfront debulking surgery in HGSC . With the availability of new treatment options such as anti‐angiogenic agents, polyadenosine diphosphate‐ribose polymerase (PARP) inhibitors, hormone receptor modulators, immune check‐point inhibitors and therapeutic vaccines, it is increasingly important to make an early prediction of tumour response to NACT.…”

Section: Crs In High Grade Serous Tubo‐ovarian Carcinoma (Hgsc)mentioning

confidence: 99%

Role of the pathologist in assessing response to treatment of ovarian and endometrial cancers

Williams

Ganesan

2019

Histopathology

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Standardisation of pathological evaluation of tissue responses to therapy permits robust stratification of patient outcomes for management decisions and allows comparison of results across clinical trials. In gynaecological pathology there are two major areas where pathological assessment of treatment response is currently used to determine ongoing therapy. High‐grade serous carcinoma (HGSC) of tubo‐ovarian origin frequently presents as high‐stage disease and may be managed by neoadjuvant chemotherapy with debulking surgery. The chemotherapy response score (CRS) is a reproducible, validated three‐tiered morphological scoring system to assess the response of HGSC to treatment. Interobserver agreement is shown to be substantial following online training, and women with CRS3 have significantly improved progression‐free and overall survival. Low‐grade endometrioid endometrial cancer and atypical hyperplasia/endometrioid intraepithelial neoplasia may be managed by progestogenic therapy in women who wish to preserve fertility or for whom medical co‐morbidities preclude surgical management. The response to treatment is assessed histologically in successive endometrial biopsies. The histological parameters are well described, but the pathological classification of treatment response is still under development. Pathological assessment of the response to treatment is incorporated into clinical guidelines.

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Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials

Cited by 200 publications

References 17 publications

Role of M1-polarized tumor-associated macrophages in the prognosis of advanced ovarian cancer patients

Role of M1-polarized tumor-associated macrophages in the prognosis of advanced ovarian cancer patients

The Chicago Consensus on peritoneal surface malignancies: Management of ovarian neoplasms

Role of the pathologist in assessing response to treatment of ovarian and endometrial cancers

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